Stewart P W, Blaine C, Cohen M, Burright R G, Donovick P J
Department of Psychology, State University of New York at Binghamton 13902, USA.
Physiol Behav. 1996 Apr-May;59(4-5):849-55. doi: 10.1016/0031-9384(95)02185-x.
We investigated the effect of chelating agent meso-2,3 dimercaptosuccinic acid (DMSA) on spatial learning and forced-swim immobility in Binghamton Heterogeneous Stock (HET) mice. Forced-swim immobility (characterized by increasingly frequent bouts of complete motionlessness in a forced-swim test, i.e., behavioral despair) is reduced by exposure to lead. In Experiment 1, male and female HETs (n = 81) were assigned to lead-exposed (0.5% lead acetate ad lib in drinking fluid), pair-fed (PF), or water control groups. Six weeks after the termination of lead exposure, half of each group was injected intraperitoneally (IP) with 50 mg/kg DMSA or vehicle once per day for 5 days. Following treatment, all animals were tested for acquisition and extinction in the Morris Water maze, followed by immobility testing in an inescapable forced-swim task. Neither Pb nor DMSA affected Morris maze performance. However, consistent with previously published work, Pb reduced immobility in the forced-water swim relative to both PF and water controls. Additionally, lead-exposed males, but not females, showed sustained improvement following DMSA treatment on immobility measures. Experiment 2 was designed to demonstrate the effect of the above DMSA protocol on blood-Pb, and also examined the immediate effects of DMSA on immobility during treatment. Thus, in Experiment 2, animals were exposed to an identical Pb and DMSA treatment protocol, but the effects of DMSA on immobility during the course of DMSA treatment were measured, and animals were sacrificed immediately after treatment so that blood-Pb measures could be taken. Under these circumstances, DMSA markedly reversed the lead-induced reduction in immobility immediately during the treatment phase. Although DMSA clearly reduced blood-lead in males, its influence on female blood levels was far less. Taken together, the data from these experiments suggest that DMSA ameliorates lead-induced immobility changes in mice, but that gender may modulate DMSA's effect on blood-lead and longer-term behavioral effects. However, further work is needed to clarify the role of gender in response to DMSA.
我们研究了螯合剂内消旋-2,3-二巯基丁二酸（DMSA）对宾厄姆顿异质种群（HET）小鼠空间学习能力和强迫游泳不动时间的影响。强迫游泳不动时间（其特征是在强迫游泳试验中完全静止不动的发作频率越来越高，即行为绝望）会因接触铅而降低。在实验1中，将雄性和雌性HET小鼠（n = 81）分为铅暴露组（饮水中自由摄取0.5%醋酸铅）、配对喂养组（PF）或水对照组。铅暴露终止六周后，每组中的一半小鼠每天腹腔注射（IP）50 mg/kg DMSA或溶剂，持续5天。治疗后，对所有动物进行莫里斯水迷宫中的习得和消退测试，随后在不可逃避的强迫游泳任务中进行不动时间测试。铅和DMSA均未影响莫里斯迷宫表现。然而，与先前发表的研究一致，相对于PF组和水对照组，铅降低了强迫水泳中的不动时间。此外，铅暴露的雄性小鼠而非雌性小鼠，在DMSA治疗后，其不动时间测量指标显示出持续改善。实验2旨在证明上述DMSA方案对血铅的影响，并研究DMSA在治疗期间对不动时间的即时影响。因此，在实验2中，动物接受相同的铅和DMSA治疗方案，但测量DMSA在治疗过程中对不动时间的影响，并在治疗后立即处死动物以便测量血铅。在这些情况下，DMSA在治疗阶段立即显著逆转了铅诱导的不动时间减少。虽然DMSA明显降低了雄性小鼠的血铅水平，但其对雌性血铅水平的影响要小得多。综合来看，这些实验的数据表明，DMSA可改善铅诱导的小鼠不动时间变化，但性别可能会调节DMSA对血铅和长期行为效应的影响。然而，需要进一步的研究来阐明性别在对DMSA反应中的作用。
